Brief Summary: This randomized phase I trial studies the side effects and best dose of endoxifen hydrochloride in treating participants who are undergoing breast surgery. Endoxifen hydrochloride may treat or reduce the risk of breast cancer.

Detailed Description: PRIMARY OBJECTIVE: I. To establish the dermal tolerability and safety of endoxifen hydrochloride (endoxifen \[ENX\]) gel administered topically to both breasts at two doses: 10 mg daily (5 mg per breast) and 20 mg daily (10 mg per breast) in comparison to vehicle placebo gel, using objective assessments based on Common Terminology Criteria for Adverse Events (CTCAE) criteria. SECONDARY OBJECTIVES: I. To measure the breast tissue concentrations of (E) and (Z) isomers of N-desmethyl-4-hydroxytamoxifen (ENX) and 4-hydroxytamoxifen (4-OHT) at each dose (10 mg per day and 20 mg per day). II. To measure the plasma concentrations of (E) and (Z) isomers ENX and 4-OHT at each dose (10 mg per day and 20 mg per day). III. To measure serum estrogenic response to topical ENX gel therapy in comparison to vehicle placebo gel (sex hormone binding globulin and insulin-like growth factor \[IGF\] pathway proteins). IV. To assess changes in coagulation parameters (factor VIII, factor IX, vWF, protein S) in response to ENX gel therapy in comparison to vehicle placebo gel. V. To assess symptoms related to use of endoxifen gel in comparison to vehicle placebo gel, as assessed by the Breast Cancer Prevention Trial (BCPT) Eight Symptom Scale (BESS) questionnaire. EXPLORATORY OBJECTIVE: I. Using pathological lesion-matched pre- and post-therapy tissue samples, to explore the potential therapeutic effects of the two doses of ENX gel in comparison to vehicle placebo gel: a) by IHC, Ki67 labelling (for cell proliferation), estrogen receptor (ER), progesterone receptor (PR) expression (for estrogen blockade); b) by expression of a panel of genes reported to change with ENX exposure (using nanostring assays). OUTLINE: Participants are randomized in Cohorts 1 and 2. All subjects in Cohort 3 will receive active agent. COHORT I: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. COHORT II: Participants apply placebo to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. COHORT III: Participants apply endoxifen hydrochloride gel to both breast skin and keep it untouched over at least 4 hours once daily for 21-28 days before breast surgery. After completion of study treatment, participants are followed up at 60 days.